TMEM173 saRNA Compositions and Methods of Use

Abstract

The disclosure relates to a saRNAs useful in upregulating the expression of a target gene and therapeutic compositions comprising the saRNA, wherein the target gene is TMEM173. Methods of using the saRNA and the therapeutic compositions are also provided.

1 . A synthetic isolated small activating RNA (saRNA) which up-regulates the expression of a target gene, wherein the target gene is TMEM173,
 wherein the saRNA comprises an antisense strand that is at least 80% complementary to a targeted sequence of the target gene, wherein the targeted sequence is selected from the group consisting of SEQ ID NO:2-15, and   wherein the antisense strand has 14-30 nucleotides.   
     
     
         2 . The saRNA of  claim 1 , wherein the antisense strand comprises a sequence selected from SEQ ID NO: 30-43. 
     
     
         3 . The saRNA of  claim 2 , wherein the antisense strand comprises a 3′ overhang. 4 The saRNA of claim  3 , wherein the 3′ overhang is uu, UU, or UUU. 
     
     
         5 . The saRNA of claim  4 , wherein the antisense strand comprises a sequence selected from SEQ ID NO: 69-82. 
     
     
         6 . The saRNA of any of  claims 1-5 , wherein the saRNA is double stranded and further comprises a sense strand. 
     
     
         7 . The saRNA of  claim 6 , wherein the sense strand comprises a sequence selected from SEQ ID NO: 16-29. 
     
     
         8 . The saRNA of  claim 7 , wherein the sense strand comprises a 3′ overhang and/or a 5′ overhang. 
     
     
         9 . The saRNA of  claim 8 , wherein the 3′ overhang is uu, UU, or UUU. 
     
     
         10 . The saRNA of  claim 8 , wherein the 5′ overhang is dT, ddT, inv ddT or invAb. 
     
     
         11 . The saRNA of  claim 8 , wherein the sense strand comprises a sequence selected from SEQ ID NO: 44-68. 
     
     
         12 . The saRNA of any of  claims 1-11 , wherein the saRNA comprises at least one modification. 
     
     
         13 . The saRNA of  claim 1 , wherein the saRNA is TMEM173-Pr-70-invAb-Se-m1 or TMEM173-Pr-70-m1-emod51. 
     
     
         14 . A pharmaceutical composition comprising the saRNA of any of  claims 1-13  and at least one pharmaceutically acceptable excipient. 
     
     
         15 . A method of up-regulating the expression of a target gene, wherein the target gene is TMEM173, comprising administering the saRNA of any of  claims 1-13 . 
     
     
         16 . The method of  claim 15 , wherein the expression of the target gene is increased by at least 30%, 40%, or 50%. 
     
     
         17 . A method of treating cancer of a subject in need thereof, comprising administering a therapeutically effective amount of the saRNA of any of  claims 1-13  or the pharmaceutical composition of  claim 13  to the subject in need thereof. 
     
     
         18 . The method of  claim 17 , wherein the cancer is a solid tumor. 
     
     
         19 . The method of  claim 18 , wherein the cancer is hepatocellular carcinoma, pancreatic cancer, or ovarian cancer.